1-169569228-G-A

Position:

• chr1-169569228-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000130.5(F5):​c.373+2993C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 151,862 control chromosomes in the GnomAD database, including 4,338 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.20 (4338 hom., cov: 33)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.377

Genes affected

F5 (HGNC:3542): (coagulation factor V) This gene encodes an essential cofactor of the blood coagulation cascade. This factor circulates in plasma, and is converted to the active form by the release of the activation peptide by thrombin during coagulation. This generates a heavy chain and a light chain which are held together by calcium ions. The activated protein is a cofactor that participates with activated coagulation factor X to activate prothrombin to thrombin. Defects in this gene result in either an autosomal recessive hemorrhagic diathesis or an autosomal dominant form of thrombophilia, which is known as activated protein C resistance. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F5	NM_000130.5	c.373+2993C>T		intron_variant		ENST00000367797.9	NP_000121.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F5	ENST00000367797.9	c.373+2993C>T		intron_variant		1	NM_000130.5	ENSP00000356771	P2
F5	ENST00000367796.3	c.373+2993C>T		intron_variant		5		ENSP00000356770	A2

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29653 AN: 151744 Hom.: 4334 Cov.: 33

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.0877

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0321

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.176

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.195 AC: 29675 AN: 151862 Hom.: 4338 Cov.: 33 AF XY: 0.187 AC XY: 13910 AN XY: 74218

Gnomad4 AFR AF: 0.415

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.0877

Gnomad4 EAS AF: 0.000966

Gnomad4 SAS AF: 0.0319

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.174

Alfa AF: 0.133 Hom.: 841

Bravo AF: 0.210

Asia WGS AF: 0.0440 AC: 153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.1
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9287095; hg19: chr1-169538466;